Yoshida, K. - Gout and Cardiovascular Comorbidities: Disentangling the Interplay with Advanced Methods to Address Measurement Issues. -- 2019-11-01 PROJECT SUMMARY Candidate: I am an Associate Epidemiologist and Instructor in Medicine in the Section of Clinical Sciences, Division of Rheumatology, Inflammation, and Immunity at Brigham and Women?s Hospital (BWH) and Harvard Medical School (HMS). My long-term goal is to develop an independent research career as a patient-oriented researcher contributing to the methodological advancement of clinical research in rheumatic diseases. I have a track record in the application, development, and dissemination of rigorous quantitative methodologies. My background includes clinical rheumatology, pharmacoepidemiology, and biostatistics. This mentored research experience will integrate my methodological research skills into clinical research focusing on gout and cardiovascular (CV) comorbidities. I will receive mentorship from Dr. Daniel H. Solomon, an established patient outcomes researcher with expertise in rheumatic diseases, including gout, as well as a team of expert co-mentors consisting of Drs. Robert J. Glynn (methodology), Brendan M. Everett (CV epidemiology), and Hyon K. Choi (gout epidemiology). Environment: I have strong support from my Department and Division at BWH, which ensures 85% protected time for the stated project for research and career development activities related to the proposed project during the 5- year award period. I have financial support to supplement my salary and research-related expenses from the Divi- sion, the Section, and my primary mentor?s funding. I have access to high-performance computing resources through BWH and HMS, as well as access to the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) data through Dr. Glynn?s support. The Partners Research Patient Data Registry enables Medicare claims linkage and targeted enrollment of gout patients for patient surveys. Research: The overarching goal of the project is to apply, develop, and disseminate state-of-the-art quantitative methods to address measurement issues frequently encountered in rheumatology, and more specifically in gout. Three related clinically important questions are drawn from the interplay of gout and comorbidities; all three aims assess the impact of measurement issues. Aim 1 on ?the cross-sectional association of gout and CV comorbidities? critically assesses the impact of misclassification in understanding the population burden of gout and CV comor- bidities. Aim 2 on ?causal investigation of gout and CV events? rigorously quantifies the influence of mismeasure- ment of gout flares and inflammatory biomarkers in mediation analysis of the potential causal link between serum uric acid and subsequent CV events. Aim 3 on ?patient-centered consideration of gout and CV disease burden? formally evaluates the validity of existing multimorbidity indices in measuring the lived experience of patients with gout, represented through patient-reported outcomes. For my first R01, I plan to develop and validate an automated multimorbidity index estimator for routine care data in the electronic health record, utilizing the knowledge and skills in mismeasurement correction obtained in Aims 1 and 2 as well as preliminary data from linked datasets (routine data and patient survey) built in Aim 3. 1